Up-regulation of connexin-43 expression in bone marrow mesenchymal stem cells plays a crucial role in adhesion and migration of multiple myeloma cells
Up-regulation of connexin-43 expression in bone marrow mesenchymal stem cells plays a crucial role in adhesion and migration of multiple myeloma cells
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DOI：
10.3109/10428194.2014.913289
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发表时间：
2015-01
影响因子：
2.6
通讯作者：
Xiao-hui Zhang;Yu Sun;Zi-yan Wang;Zhanping Huang;Bingzong Li;Jin-xiang Fu
中科院分区：
文献类型：
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作者：
Xiao-hui Zhang;Yu Sun;Zi-yan Wang;Zhanping Huang;Bingzong Li;Jin-xiang Fu
摘要多发性骨髓瘤(MM)细胞主要聚集在骨髓内，并与骨髓微环境密切相关。连接蛋白-43(Cx43)是存在于骨髓间充质干细胞(BMSCs)中的主要连接蛋白。我们发现，正常BMSCs表达Cx43的水平低于MM患者。BMSCs中Cx43的表达在基因和蛋白水平上均上调，与RPMI8226细胞共培养后，细胞间隙连接介导的细胞间通讯得到改善。缝隙连接阻断剂18α-甘草次酸(18α-GA)抑制MM细胞与骨髓间充质干细胞的黏附。经18α-GA处理后，骨髓间充质干细胞分泌基质细胞衍生因子-1α(SDF-1α)减少，并抑制骨髓间充质干细胞诱导的MM细胞迁移。这些结果提示，骨髓间充质干细胞中Cx43表达的改变参与了骨髓瘤细胞与骨髓环境的相互作用，并在骨髓瘤细胞的黏附和迁移中起着至关重要的作用。
Abstract Multiple myeloma (MM) cells accumulate mainly in the bone marrow (BM) and are closely related to the BM microenvironment. Connexin-43 (Cx43) is the main connexin present in bone marrow mesenchymal stem cells (BMSCs). We found that normal BMSCs expressed a lower level of Cx43 than those derived from patients with MM. Cx43 expression in BMSCs was up-regulated at both the gene and protein level, and gap junction-mediated intercellular communication was improved in BMSCs after co-culture with RPMI 8226 cells. The gap junction blocker 18α-glycyrrhetinic acid (18α-GA) inhibited the adherence of MM cells to BMSCs. Treatment with 18α-GA decreased stromal cell-derived factor-1α (SDF-1α) secretion by BMSCs and inhibited the migration of MM cells induced by BMSCs. These results suggest that alteration of Cx43 expression in BMSCs is involved in the interactions of MM cells with the BM environment and plays a crucial role in the adhesion and migration of MM cells.